Apparatus and method for implantation of devices into soft tissue

ABSTRACT

Apparatus and method for surgeon-assisted rapid surgical implantation of devices into soft tissue. The apparatus comprises several subsystems that enable the referencing of the spatial position and orientation of the device being implanted with respect to the soft tissue into which it is being implanted and then the controlled implantation of the device at a predefined speed with higher positional accuracy and precision and a reduction in soft tissue damage, provided by ultrasonic assisted motion, compared to current state-of-the-art implantation methods and devices. The method includes automated loading of the device being implanted into a clamping mechanism from a cartridge holding a number of implants, referencing of the device position and orientation, referencing of the surface of the tissue into which the device is being implanted, monitoring of the tissue motion, identification of desirable implant location based on the soft tissue profile, allowance of surgeon selection and fine adjustment of the final implant location, high-speed implantation, device release and implant actuator retraction.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Non-provisional application that claims thebenefit of U.S. Provisional Application Ser. No. 61/690,044, titledAPPARATUS AND METHOD FOR IMPLANTATION OF DEVICES INTO SOFT TISSUE, filedJun. 18, 2012, which is incorporated by reference herein.

STATEMENT REGARDING FEDERALLY-SPONSORED RESEARCH AND DEVELOPMENT

This invention was made with partial government support under DARPAgrant N660011114025. The government has certain rights in thisinvention.

FIELD OF THE INVENTION

The invention relates to apparatus and methods for the surgicalimplantation into soft tissue of devices, such as (1) prosthetic neuralinterfaces between computers and the machinery they control andbiological tissue, for example neurons and the nodes of Ranvier on axonsin nerve bundles, (2) optical fibers for the localized stimulation ofneurons and other cell types, and (3) drug delivery catheters, amongothers. The micrometer-scale interfaces being surgically implanted canbe used for recording from the soft tissue in which they are embedded orstimulating the soft tissue in which they are embedded. The inventionrelates to the accurate and minimally invasive placement of prostheticmicron-scale implants at a predetermined depth, location and orientationbased on the profile of the tissue, for example the vasculature of thebrain, and the use of implantation-specific data like soft tissuecompression force prior to penetration and frictional force between themicrometer-scale implant and the tissue after penetration to optimizefinal placement of the interface. The invention relates to the use ofultrasonic oscillatory motions superimposed on the main trajectory totailor the trajectory of the implantation to realize the reduction ininsertion forces and soft tissue compression, which prevents effectiveinsertion and increases tissue damage. The invention relates to the useof multi-unit cartridges for the implantation of multiplemicrometer-scale interfaces during a single surgery without retooling,to reduce surgery time and minimize the handling of the prostheticinterfaces. The invention also relates to precise control of insertionspeed, and tools for visual and sensor-based inspection of insertioncharacteristics such as initial tissue contact and forces duringinsertion.

BACKGROUND OF THE INVENTION

Many implantable devices that interact with tissue, including those usedin surgical procedures, in-vitro tests, and in-vivo implantations,require special care for accurate positioning (location and orientation)of the implantation device. Furthermore, a critical issue is to ensurethat implantation occurs satisfactorily; that is, the device is insertedin at the required depth without device failure. Manual insertions ofdevices cannot provide this level of control in positioning andinsertion, therefore leading to high rate of device failure duringinsertion, over-design of devices with larger-than-needed foreignmaterials, and functional failures. An important need is to haveautomated mechanisms for insertion, that provide precision inpositioning (cellular-scale, approximately 20 μm), orientation (±0.5),and speed control (±1%), as well as allow feedback and evaluationthrough visual and sensor-based in-situ characterization capability.

An illustrative example of this need arises from the insertion of theneural probes for brain-computer interfaces (BCI). Research on BCI andbrain-machine interfaces (BMI) in recent years has demonstrated thefeasibility of driving motor prostheses for the upper limbs of amputeesand for restoring mobility to quadriplegics and tetraplegics whosecondition arose due to injury or disease. More recently, research hasbegun to focus on providing feedback loops between the brain and othernervous tissue and the computers and machines to which they areinterfaced by stimulating the tissue with signals from the externalequipment to return sensation to BMI and BCI recipients. In this way, aninjured or diseased individual can control an external prosthetic andreceive sensation from it in a way that naturalistically mimics the limbthey lost or the biological function that is impaired.

BCIs and BMIs comprise: 1. an interface to the soft tissue that recordsthe electrical, chemical or mechanical activity of the soft tissue andtransduces it to a signal in a suitable energy domain, typicallyelectrical, 2. a decoder that extracts the information from the signalsreceived from the tissue, 3. a transmitter that sends out the decodedsignals, 4. a receiver of the decoded signal, 5. a computer or machinethat acts under the instructions carried in the decoded signals, 6. asensor array that detects changes in the environment caused by theaction of the computer or the machine and transduces it to a signal in asuitable energy domain, 7. an encoder that receives the output of thesensor array and converts it to a sensory signal for transmission, 8. atransmitter that sends out the encoded sensory signals, 9. a receiver ofthe encoded sensory signals, and 10. an interface that transduces theencoded sensory signals to an electrical, chemical or mechanical signalfor stimulation of the soft tissue in which the interface is embedded.

The interface is a critical feature of BMIs and BCIs and its placementmust be as close as possible to the biological signal sources withoutdamaging them in order to maximize the information extracted from thesoft tissue and minimize the amount of energy needed to transmit sensoryinformation back into the soft tissue. The most common interface is theelectrode. Typically, this is an insulated, electrically conductivematerial with a small surface exposed to the soft tissue environment.Electrodes have dimensions ranging from 10s of micrometers to 100s ofmicrometers. The effectiveness, stability and reliability of theseinterfaces has been identified in the literature, in part, as dependenton the method of implantation and the accuracy of their placement.Interface reliability is a critical research area where progress isneeded prior to transitioning BMI and BCI technology for practicalrestoration of motor and sensory functions in humans. Two key issuesare 1) the inability of current interfaces to reliably obtain accurateinformation from tissue over a period of decades, and 2) currentlymeasured signals from tissue cannot be reliably used to control highdegree-of-freedom (DOF) prostheses with high speed and resolution.

Failure of biological soft tissue interfaces may be caused by severalissues. After implantation, current probes are surrounded by reactivemicroglia and reactive astrocyte scarring as shown pictorially in FIG.1(a). In the brain, damage to the neural vasculature causes a breach inthe blood-brain barrier (BBB) that is associated with reactive softtissue responses. Tissue reaction with the probe results inencapsulation that insulates the electrode by impeding diffusion ofchemical and ionic species and may impede current flow from the softtissue to the interfaces. Encapsulation increases the distance of theelectrode from active neurons. For viable recording, the distance of theelectrode from active neurons must be less than 100 μm. Progressivedeath and degeneration of neurons in the zone around the inserted probedue to chronic inflammation may eliminate neural electrophysiologicalactivity. Lastly, interconnects may fatigue and break due to stresses.Experiments in animals have resulted in some neural electrode sitesfailing while others keep working for several years. This variability inoutcome is believed to be due to several factors including variable BBBdamage, variable scar formation, mechanical strain from micromotion,inflammation, microglial condition and disconnected neurons.

Tissue interfaces employed today for BMI and BCI applications come in avariety of shapes made of many materials and apparatus and methods forimplanting these interfaces must have the functional and designflexibility to handle the multiplicity of devices available today andaccommodate the designs and forms that become dominant as the technologymatures and moves into widespread human use. In the next few paragraphs,the challenge presented by the range of device types and materials willbe established by reviewing the devices described in the literature.

Historically, the interfaces have been stiff needles usually made fromwires, silicon or glass. Metal wire neural probes are typically 50-100μm in diameter and usually made of platinum or iridium and insulatedwith glass, Teflon, polyimide or parylene.

Silicon-mounted interfaces made with MEMS fabrication were firstintroduced by Ken Wise and Jim Angell at Stanford in 1969. Ken Wise'sgroup at the University of Michigan subsequently developed a series ofsilicon probes and probe arrays with multi-site electrodes.

A 2D probe array was developed at the University of Utah in 1991, knownas the Utah Electrode Array (UEA). The UEA has become a favoredinterface in human applications in the central nervous system (CNS) andfor research in the peripheral nervous system (PNS).

Polycrystalline diamond (poly-C) probes with 3 μm thick undoped poly-Con a ˜1 μm SiO₂ layer have been fabricated by Dr. Aslam's group atMichigan State University.

Research groups have created more compliant probes made with thin-filmwiring embedded in polymer insulating films. Flexible CNS probes havebeen made in polyimide, SU8/parylene and all parylene. These probes arestill extremely stiff in both axial and transverse directions relativeto brain tissue, which has a Young's modulus of approximately 30 kPa.Any axial force transmitted through the external cabling directly actson the probe and creates shear forces at the electrode-tissueinterfaces. Such forces may come from external motion or from tissuegrowth around the implant. To address this issue, a group from CarnegieMellon University and the University of Pittsburgh have developed aparylene-coated Pt probe with a thickness of 2.5 μm and width 10 μm thatprovides axial strain relief in the brain through a meandered design(FIG. 1(b)). The cables external to the brain are also meandered tofurther reduce transmission of brain-skull relative motion to theembedded probe. Because of the size and compliance of the meanderedprobes they are embedded in a biodissolvable delivery vehicle whichprovides the stiff structure for implantation.

A team from Drexel Univ., the Univ. of Kentucky and SUNY createdceramic-based multisite microelectrode arrays on alumina substrates withthickness ranging from 38 to 50 μm, platinum recording sites of 22 μm×80μm, and insulation using 0.1 μm ion-beam assisted deposition of alumina.

Y.-C. Tai's group at Caltech produced parylene-coated silicon probeswith integral parylene cabling, shown in FIG. 2(a). The shanks were upto 12 mm long. A primary innovation was a flexible 10 μm-thick, 830μm-wide, 2.5 mm-long parylene cable.

Flexible polyimide probe arrays (FIG. 2(c)) have been made with goldelectrodes. These probes must be inserted by first creating an insertionhole with a scalpel or needle. A later polyimide probe arrayincorporated silicon for selected locations along the length of theshank, with polyimide connectors to create enhanced compliance, as shownin FIG. 2(b).

An innovative all-polymer probe design incorporated a laterallattice-like parylene structure attached to a larger SU8 shank to reducethe structural size close to the electrodes. The lattice structure,shown in FIG. 2(e), included a 4 μm-wide, 5 μm-thick lateral beamlocated parallel to the main shank. Encapsulating cell density aroundthe lateral beam was reduced by one-third relative to the larger shank.While the structure was non-functional, it is presumed that placingelectrode sites on the smaller beam would result in superior recordingperformance.

U.S. patent application 20090099441 from Dr. Giszter's Drexel groupdescribes biodegradable stiffening wires 1 braided with electrode wires2 (see FIG. 2(f)) where flexible wires 2 are braided onto a maypolestructure 4 with stiff biodegradable strands 1. When the biodegradablestrands 1 dissolve, the flexible wiring 2 is left in the brain tissue.These braided composite electrodes are similar in spirit to presentinvention. However, reliable and manufacturable connections to thebraided wires become difficult when scaled to arrays.

Olbricht et al has reported on flexible microfluidic devices supportedby biodegradable insertion scaffolds for convection-enhanced neural drugdelivery. The device consists of a flexible parylene-C microfluidicchannel that is supported during its insertion into tissue by abiodegradable poly(DL-lactide-co-glycolide) (PLGA) scaffold. Thescaffold is made separately by hot embossing the PLGA material into amold.

Tyler et al, have developed a neural probe made from a polymernanocomposite of poly(vinyl acetate) (PVAc) and tunicate whiskers,inspired by the sea cucumber dermis. The probe material exhibits a realpart of the elastic modulus (tensile storage modulus) of 5 GPa afterfabrication. When exposed to physiological fluid conditions, its modulusdecreases to 12 MPa.

The trend in devices is towards more compliant materials and structuresthat will have stringent implantation requirements in terms of speed,force and placement. In the following paragraphs, the state-of-the-artin soft tissue interface insertion technology is described.

Manual implantation or stereotaxic assisted implantation by a skilledsurgeon is the most common method of implantation of the variety ofinterfaces and interface delivery vehicles described above. Manualimplantation means the procedure is done by hand and stereotaxicassisted implantation means it is done through the use of a stereotaxicframe that holds the interface delivery vehicle and provides a handoperated screwdrive to position and insert the interface. Positioning isusually performed with the assistance of a stereomicroscope thatprovides some measure of depth perception. With this technique, there isno control over the speed of insertion and only gross sensitivity to theprofile of the underlying soft tissue, both of which could contribute tothe variability observed in the outcomes of soft tissue interfaceimplantations. Insertions of the Michigan probe array are done usingthis method.

The low velocity of manual insertions, either by hand or usingstereotaxic frames, results in observable soft tissue dimpling prior topenetration of the tissue. Dimpling was found to be accompanied by softtissue compression that resulted in damage to the tissue and reducedsignal extraction.

To improve outcomes by reducing manual variability and increasinginsertion speed, research groups adopted a hand-held pneumatic insertiondevice invented by Normann et al. and experimentally demonstrated byRousche and Normann. The pneumatic inserter has a piston mechanism thatis actuated pneumatically to strike an endpiece rod on which is adheredthe device to be implanted. The burst of pressure accelerates the pistonand its momentum is transferred to the endpiece rod which is driventoward the brain at speeds of 8 m/s, which was found to be required forthe 10 electrode×1 electrode interface to penetrate the soft tissue. Anadverse effect of the mechanism is recoil of the endpiece due to thereturn spring which can lead to retraction of the interface device if itremains adhered to the endpiece. Researchers using the UEA avoid thiseffect by resting the interface on the tissue into which it will beimplanted and using the endpiece to strike the back of the interfacedevice. This technique does not allow for accurate placement of theinterface in soft tissue because there is no visibility of the contactpoints between the interface and the tissue. House et al. achieved ameasure of control over the spatial relationship between the endpieceand the device to be inserted by mounting the pneumatic inserter on astereotaxic manipulator. They found the impact between the endpiece andthe backside of the interface often led to damage of the interface, sothey added a “footplate” to the device. However, because the device isnot mechanically connected to a fixed reference structure, it is subjectto elastic recoil from the soft tissue into which it is implanted andthis can lead to retraction of the interface from the tissue. Toovercome retraction the interface must be over-driven into the softtissue so that after recoil, the full length of the interface remains inthe tissue. The literature does not have detailed studies on the impactof over-driving the insertion on the health of the recipient.

The literature reports other insertion mechanisms of varying levels ofcomplexity and functionality. Rennaker et al. reported a manuallypositioned spring-driven hammer mechanism for insertions up to 1.5 m/sfor microwires mounted on the insertion device using a locking screw.Jensen et al. reported a hydraulically driven micromanipulator withmanual positioning and force sensing and a speed of 2 mm/s. Dimaio andSalcudean used a robotic manipulator to implant 17 gauge epiduralneedles with force sensing but did not report the insertion speeds theyachieved. Bjornsson et al. used stepper motors to implant Simicroneedles at up to 2 mm/s with force sensing. Sharp et al.electronically controlled a micromanipulator with an in-line load cellto achieve insertion speeds from 11 μm/s to 822 μm/s for evaluation ofpenetration mechanics in cerebral cortex. In each of these cases andothers in the literature, fine positioning, if done, was performed byvisually locating the interface over the soft tissue to be implanted.

Accurate placement of the interface requires referencing of the tissueheight, maintaining the relative height between the interface mounted onthe insertion apparatus and the tissue as the tissue surface moves underpulsatile and respiratory motion, mapping and identifying the insertionlocation with an overlay of the interfaces and positioning the interfacein space with respect to the tissue surface. This is an area where theliterature is very sparse. Kozai et al. used two photon imaging to mapthe cortical vasculature to identify target locations prior to interfaceimplantation and found that when this is done the trauma of implantationcan be reduced by 73% for surface vasculature compared to the case whenvasculature is targeted.

SUMMARY OF THE INVENTION

The present invention describes an apparatus and method for implantingdevices into soft tissue with accuracy and precision in three dimensionsas well as in prescribed insertion speed and trajectory, and reduces thedamage that occurs to the soft tissue into which the device isimplanted.

The invention apparatus comprises several sub-systems that provide thefunctionality to achieve accuracy, precision and damage reduction. Thesesubsystems are: 1. an actuator, such as the M272 piezo motor sold by PIof Auburn, Mass., that moves at a controlled high velocity along asingle, longitudinal axis (i.e the implantation trajectory) with a largetravel range up to 50 mm and better than 20 micron positional accuracy;2. an actuator, such as that made from K-740 PZT by Piezo Technologies,Indianapolis, Ind. that can impart an oscillatory motion at frequenciesbetween 18 kHz and 30 kHz in two directions, corresponding to thetransverse directions to the insertion direction, or the single,longitudinal axis) for reduction of insertion forces; 3. a load cell,such as the Sensotec Model 31 sold by Honeywell of Morristown, N.J.,that measures the force between the device being implanted and thetissue surface during implantation; 4. a contact sensor for accuratedetection of the point and time of contact between the soft tissue andthe device being implanted, which can be achieved by monitoring theelectrical characteristics of the piezo-actuator described in subsystem2; 5. a laser ranging system, like the Hokuyo URG-04LX-UG01 with aSokuiki sensor, for referencing the position and motion of the tissuewith respect to the insertion system and the device being implanted; 6.an imaging system, such as the SE-1008-400X video microscope fromSelectech Electronics of Guangdong, China, for identifying the optimalinsertion location to minimize mechanical damage to tissue vasculature;7. a clamping mechanism, such as an MGP800 series clamp from SommerAutomatic of Ettlingen, Germany, to hold the device being implanted,that is operated in coordination with the actuator; 8. a set of clampingsurfaces with a design that is customized to the form of the devicebeing implanted; 9. a cartridge for holding multiple devices with adesign that is customized to the form of the device being implanted; 10.a dispenser that moves devices from the cartridge to the clamp, with adesign that is customized to the form of the device being implanted, oran operating sequence in which the cartridge is stationary and theactuator and clamp execute a predefined sequence to move to the nextdevice to be implanted and pick it up in the clamp; and 11. the actionof the system and its various subsystems are coordinated using softwaresuch as Labview from National Instruments of Austin, Tex. which canprovide a graphical user interface for ease of use, data acquisitionfrom the various subsystems for real-time monitoring of the insertionprocedure and offline analysis for diagnostic and clinical evaluation. Asoftware like Matlab's Image Processing module from Mathworks of Natick,Mass., can provide the capability of capturing and manipulating imagedata and processing them according to a variety of algorithms thatidentify sensitive tissue structures, overlay images of the implantationsites and compute overlap area of sensitive tissue structures andimplantation sites.

The method of the invention in summary is: 1. device loading; 2. devicereferencing; 3. implantation location identification; 4 optional surgeonfinal adjustment; 5. tissue height referencing; 6. implantation; 7.device release; and 8. actuator retraction.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B show schematics of soft tissue reactions to animplantable device in neural tissue based on its dimensions;

FIGS. 2a-f show a variety of implantable devices to illustrate the rangeof shapes and sizes the implantation apparatus must be capable ofhandling;

FIG. 3 shows one embodiment of an apparatus for the implantation ofdevices into soft tissue;

FIGS. 4A and 4B show the displacement vs. time trajectory of the deviceduring implantation with a small amplitude ultrasonic oscillation invarious planes overlaid on it;

FIG. 5 shows schematic drawings of an embodiment of the apparatus withall sub-systems shown;

FIGS. 6A, 6B and 6C show schematic drawings of the referencing procedurefor device and tissue surface and the translation and rotation of theactuator from its initial location to its optimal location;

FIGS. 7A and 7B show an image of the surface of the field of view of animplantation location in the brain and a virtual representation of theimplantation sites overlaid on the surface of the brain.

FIG. 8 shows an open section of a cartridge for holding a number ofdevices in preparation for implantation;

FIGS. 9 A and B show side views and face views of each side of clampingjaws used to hold the devices to be implanted;

FIG. 10 is a process flow diagrams of an exemplary process of thepresent invention in which the device to be implanted is loaded onto anactuator and referenced for implantation into soft tissue;

FIGS. 11A and 11B is a process flow diagram of an exemplary process ofthe present invention in which the optimal implantation location for thedevice being implanted is identified;

FIG. 12 is a process flow diagram of an exemplary process of the presentinvention in which signals from force and contact sensors are used asfeedback to modify the trajectory of the actuator implanting the deviceinto tissue;

FIG. 13 is a process flow diagram of and exemplary process of thepresent invention in which the system is operated at a high level

FIG. 14 is a block diagram illustrating the interconnection andfunctional relationships between the components and sub-systems of theapparatus

DETAILED DESCRIPTION OF THE INVENTION

The present invention addresses the problem of the accurate and preciseplacement and depth of devices implanted into human tissue with reducedsoft tissue damage. Now turning to FIGS. 5 and 14, the present inventionis an apparatus 10 for holding, referencing, targeting, and implantingdevices of various sizes, shapes and materials into soft tissue and themethod that must be followed for the achievement of accuracy, precisionand reduced damage using the apparatus. The apparatus 10, by way ofrepresentation and not invention limitation, can include an actuator 12,laser ranging sub-system 30, contact sensor 16, load cell 20, imagingsub-system 28, clamp mechanism 18 with clamp surface 22, processor 40,memory 42, and display 44 for implantation of device 14 into tissuesurface 32 (FIG. 6B) of a patient. The high level operation of theapparatus and the method for executing implantations is detailed in theprocess flow diagram in FIG. 13. The step numbers are labels and are notnecessarily in ordered sequence in relation to other figures, unlessthere is an express indication that two or more figures are related (forexample, FIGS. 11A and 11B).

Step 38: Prepare the patient surgically for device implantation bymaking an incision in the body and exposing the implantation vicinity ina tissue of interest.

Step 39: Position the apparatus 10 in proximity of the patient.

Step 40: Power on the apparatus 10 and configure it for the tissue typeinto which the device 14 will be implanted (for example, neural tissuein the brain), including entering the device implantation depth into theapparatus.

Step 41: Load the dispense cartridge sub-system 25 with the devices 14to be implanted (FIG. 8).

Step 42: Load a device 14 to be implanted into the clamp surface 22(FIG. 8).

Step 43: Reference the height D₂ of the device 14 to be implanted (FIG.6A).

Step 44: Position the device 14 to be implanted above the incision thatdefines the implant vicinity (FIG. 6B).

Step 45: Locate the optimal implant location (FIG. 7).

Step 46: Reference the tissue height (FIG. 6B).

Step 47: Implant the device 14 into the tissue surface 32.

Step 48: Open the clamp mechanism 18 and withdraw the actuator 12leaving the device 14 in the tissue.

Step 49: Are there more devices to be implanted? If yes, then go to backStep 42 repeat steps 42 to 49 until all devices are implanted. If no,then continue to Step 50.

Step 50: Shutdown the apparatus 10.

Now turning to FIGS. 3, 5, and 14, the apparatus 10 of the presentinvention comprises a number of sub-systems that serve particularpurposes in the successful achievement of accuracy, precision andreduced soft tissue damage. Each subsystem, the function it performs andits role in the implantation method is described in detail in thefollowing paragraphs.

The implantation is achieved with an actuator 12 that moves at acontrolled high velocity along a single, longitudinal axis with avariable travel range (for example, several centimeters), and highprecision and accuracy in the insertion trajectory (both displacementand velocity). For example, if the device 14 is to be implanted inneural tissue, which has the most stringent placement requirements, aplacement accuracy of <50 microns is necessary to ensure the correctcortical neuronal layer has been implanted. The implantation orientationis also critical and should be normal to the surface being implanted toensure no torque is applied to the device as it is implanted. In oneembodiment, an orientation accuracy of ±1° to normal is preferred in thecase of micron-scale, needle-shaped devices. In one embodiment of theinvention (See FIG. 3), the actuator 12 is a piezomotor (like the PIM272 with a maximum velocity of 200 mm/s and a force output of 8 N) butit can be substituted with a screw-drive, a stepper motor, or anotheractuator (linear and/or rotational) depending on the force and velocityconditions required by the device implantation. Attached to the actuator12 is a load cell 20 for sensing the force on the device 14 beingimplanted during the implantation procedure, a contact sensor 16 fordetecting contact between the device 14 being implanted and thereferencing tab 24 (FIG. 6A) or the tissue surface 32 (FIG. 6B), andcontact been the clamping mechanism 18, that holds the device 14, andthe referencing tab 24 (FIG. 6A) or the tissue surface 32 (FIG. 6B),during the referencing and implantation procedure. The dispensecartridge sub-system 25 that holds the devices 14 prior to loading intothe clamping mechanism 18 is shown in FIG. 8 as a standalone component,but could be integrated into the actuator or another part of the system.The actuator 12 in some embodiments is capable of moving with a smallamplitude ultrasonic oscillation overlaid on the implantation trajectory(See FIG. 4a ). The force of implantation of a micron-scale device 14,like the devices that this apparatus 10 will be used to implant, can bereduced by applying ultrasonic oscillations in the range from 18 kHz to30 kHz during implantation into soft tissue. The oscillation can beeither in the direction parallel to the implantation trajectory (i.e.longitudinal), or it could be parallel to the plane of the surface ofthe tissue being implanted (i.e. transverse) (See FIG. 4b ), Additionalultrasonic actuators can be added to achieve the oscillation, or theoscillation could be generated by modifying the drive signal of theimplantation actuator to include, for example, an overlaid sinusoidal orstep signal 12.

Attached to the actuator 12 is a clamping mechanism 18, which can beelectrically, pneumatically or magnetically driven, depending on theembodiment. In the particular embodiment shown in FIG. 3, the clampingmechanism 18 is a Techno Sommer MGP800 series pneumatic clamp. Theclamping mechanism 18 has clamping jaws 22 mounted to it that is used tohold the device 14 being implanted so that it cannot change its spatialposition and orientation during referencing and targeting. The processflow of loading and referencing the device 14 to be implanted is shownin FIG. 10:

Step 1: Initialize the apparatus 10 to bring all mechanical axes totheir home position (initial horizontal and initial vertical positions);

Step 2: Move the actuator 12 to the horizontal position of the firstdevice 14 in the dispense cartridge sub-system 25;

Step 3: Open the clamping jaws 19;

Step 4: Move the actuator 12 through the vertical distance between theactuator 12 and the dispense cartridge sub-system 25;

Step 5: Close the clamping jaws 19 to hold the device 14 (FIG. 8);

Step 6: Withdraw the actuator 12 to its initial vertical position;

Step 7: Move the actuator 12 to the horizontal position of the heightreference tab 24 (FIG. 6A);

Step 8: Move the actuator 12 in the vertical direction until contactbetween the device 14 and the reference tab 24 is detected;

Step 9: Store the vertical position at which contact with the referencetab 24 was detected; and

Step 10: Return the actuator 12 to its initial vertical height andhorizontal position.

The various in-plane motions described in FIG. 10 and hereafter are tobe understood by those versed in the art as being executed by roboticactuators with limit stops or manually through the use of locating pins.

Now turning to FIGS. 9A and 9B, the clamping jaws 22 can be formed froma number of different materials, depending on the application. In theparticular embodiment shown in FIG. 3, the clamping jaws 22 are made ofstainless steel, but materials of varying stiffness could be used. Theclamping jaws 22 have two clamping surfaces 19 on opposing faces of eachjaw 22 as shown in FIG. 9a and FIG. 9b . Each clamping surface 19 hascontours 34 that are designed to fix the position and orientation of thedevice 14 to be implanted while it is penetrating the tissue into whichit is being implanted to minimize relative motion of device 14 withinclamping jaw 22. On one clamping surface 19, the contour 34 is a recess36 (FIG. 9a ) and on the other face the contour 34 is a protrusion 38(FIG. 9b ), wherein protrusion 38 can be received into recess 36.Alternative embodiments of the clamping surfaces 19 can include acoating with materials that would modify their surface conditions toreduce or eliminate sticking, for example Teflon. The device 14 to beimplanted can be placed manually between the clamping surfaces 19 andthe clamp mechanism 18 can be closed. Alternatively, the dispensecartridge sub-system 25 shown schematically in FIG. 8 can be used toload a single device 14 and, after the device 14 has been implanted, thenext device 14 will be automatically loaded from the dispense cartridgesub-system 25 into the clamping mechanism 18 until all the desiredimplantations are complete.

A load cell module 20, containing such load cells as the Sensotec Model31, mounted on the actuator 12 (See schematic in FIG. 5) measures theforce between the tissue and the device 14 being implanted duringimplantation. Knowledge of the force is a useful diagnostic forassessing soft tissue damage and implantation success and can be usedduring implantation as a feedback signal to control the actuator 12,either to maintain, increase or reduce the amount of force to ensureprecision in depth control.

The contact sensor 16 detects the contact of the device 14 beingimplanted with the tissue into which it is being implanted and thesignal obtained can be used to modify the implantation conditions toensure precision in depth control. For some devices 14, implantationmust be done in a single try and their tips 26, which are extremelysharp to reduce implantation force and soft tissue dimpling duringimplantation would be damaged if force feedback through the load cell 20is used to detect contact of the device 14 with a reference stage duringthe referencing operation so a sensor optimized for contact detection isrequired. Contact sensors 16, such as the ones from Kistler of Novi,Mich., have the ability to detect contact between two structures with aforce of approximately 2 mN, which is below the force level that wouldlead to damage of the tips 26 of the device 14 being implanted. In theembodiment shown schematically in FIG. 5, the contact sensor 16 ismounted on the outer side of the clamping surfaces 19 to achieve theoptimal signal to noise ratio for the contact sensor 16. After thedevice 14 being implanted is loaded in the clamping mechanism 18, theactuator 12 moves laterally or rotationally to a reference tab 24 andmoves in the implantation direction through a distance D₁ until contactwith the reference tab 24 is sensed (see schematic in FIG. 6A). Thedistance D₁ is measured through the software that controls the actuator12. The position at which contact is sensed is used as a reference forthe tip 26 of the device 14 being implanted to ensure the spatialrelationship between the device tip 26 and the tissue surface 32 it willbe implanted through is known to the positional accuracy of the actuator12 (see FIG. 12). The distance from the laser ranging system 30 to thebase of the clamp 18 is fixed by design at a distance D₄. The distancefrom the base of the clamp 18 to the recess 36 (FIG. 9A) on the clampingsurface 19 of the clamp jaws 22 is fixed by design at D₃. The distancefrom the recess 36 on the clamping surface 19 of the clamp jaws 22 tothe reference tab 24 is fixed by design at D₅. When contact between thetip 26 of the device 14 and the reference tab 24 is detected after theactuator 12 has travelled a distance D₁, the device 14 length D₂ can becalculated by D₅−D₁. After D₂ has been calculated the distance from thelaser ranging system 30 to the tip of device 26 is known (D₂+D₃+D₄).

After device referencing, the surgeon performing the implantation or aprocessor 40 executing an automated routine uses the imaging sub-system28 to position the device 14 being implanted above the tissue surfacebeing implanted (see schematic in FIG. 6B), which is shown in a processflow diagram in FIGS. 11A and 11B. It is to be understood by thoseversed in the art that the movement of the actuator 12 during theprocedure described in FIGS. 11A and 11B can be achieved usinguser-guided robotic control:

Step 11: It is assumed at this step that the actuator 12 is in itsinitial position following the procedure in FIG. 10 and that the imagingsystem 28 is in its low magnification state which can be on the order of0.5× to 5×;

Step 12: Move the actuator 12 to the implantation vicinity as determinedby a magnified video image;

Step 13: Determine the vertical distance and angular relationshipbetween the actuator 12 and the surface 32 of the tissue in theimplantation vicinity;

Step 14: Adjust the position of the actuator 12 to zero the angulardisplacement between the longitudinal axis of the actuator 12 and thenormal to the tissue surface 32 at the implantation vicinity;

Step 15: Increase the magnification to a point where the area of thespatial range of the implantation sites is 25% of the field of view 46in the video image (FIG. 7A);

Step 16: Capture an image of the tissue surface 32 in this field of view46 (FIG. 7A);

Step 17: Process the raw image of this field of view 46 to delineatetissue structures subject to damage by device implantation, based onparameters, for example the veins 48 visible in FIGS. 7A and 7B;

Step 18: Overlay on the processed image a to-scale projection of theimplantation sites 50 for the device 14 to be implanted based on thecurrent position of the actuator 12, as shown in FIG. 7B, this is theinitial implantation location;

Step 19: Compute the total area of overlap between the implantationsites 50 and the tissue structures subject to damage by device 14implantation;

Step 20: Displace the virtual representation of the implantation sites50 by a user-defined fraction of the dimension of a single implantationsite and by a user defined step angle to a subsequent implantationlocation, for example, if the implantation site is 80 microns indiameter, the horizontal displacement could be 10 microns and the stepangle (or angular displacement) could be 0.5° (see FIG. 6C for anillustration);

Step 21: Repeat Steps 19 and 20 until every horizontal and angularposition of the implantation sites in the entire field of view 46 has acomputed overlap area;

Step 22: Identify the horizontal and angular position of theimplantation sites 50 that leads to the minimum overlap area between theimplantation sites 50 and the tissue structures subject to damage bydevice implantation, this is called the optimal implantation location;

Step 23: Overlay the projection of the implantation sites 50 at theoptimal implantation location onto the live video image of the field ofview 46, overlay can be color coded for ease of recognition;

Step 24: Prompt the surgeon to accept this implantation location or makea manual adjustment of the software projection of the implantation sites50 on the live video image (optional);

Step 25: Finalize the implantation location (optional);

Step 26: Move the actuator to the optimal implantation location andoverlay the virtual representation of the implantation sites 50 on thelive video image;

Step 27: Determine the vertical distance and angular relationshipbetween the actuator 12 and the surface of the tissue at theimplantation location using the laser ranging subsystem;

Step 28: Adjust the position and orientation of the actuator so thelongitudinal axis of the actuator is normal to the tissue surface at theoptimal implantation location, based on the vertical distance andangular relationship;

Step 29: Prompt the surgeon to make a final refinement of theimplantation location, accept the current position and orientation orrestart the mapping process at Step 16 (optional); and

Step 30: Finalize the implantation location and move the actuator tothat position and orientation if a manual refinement occurred(optional).

The imaging sub-system 28, such as the Selectech SE-1008-400X videomicroscope, has a magnification range from 0.5× to 400× that enables theidentification of the implantation vicinity at low magnification and theidentification of the exact implantation location at high magnification.The implantation vicinity could correspond to a hole drilled through theskull, or a vertebra, with a scale of several millimeters in diameter.The exact implantation location could be 10's of microns in diameter anda small area within the implantation vicinity. The multiplemagnification scales are necessary to allow the surgeon doing theimplantation to locate the small implantation location within the largerimplantation vicinity. As higher magnifications also result in smallerfields of view, it is necessary to have low magnification imaging fororienting to the implantation vicinity. Through a software like Matlab'sImage Processing module, a video image of the tissue surface at theimplantation location, in the visual region of the electromagneticspectrum, or the infrared region, is captured (FIG. 7a ) and a virtualrepresentation of the initial implantation site, or sites formulti-shank devices, based on the current position of the actuator 12are overlaid on the video image of the tissue surface, as shown in FIG.7b . The laser ranging sub-system 30 references the surface of thetissue into which the device 14 is being implanted and monitors the finemotions of the tissue due to, for example, respiratory and pulsatilemotions. A laser ranging sub-system 30, such as the Hokuyo URG-04LX-UG01Sokuiki sensor, is mounted to the body of the linear actuator 12 asshown schematically in FIG. 6B. This system works by reflecting laserbeams off of the surface of the tissue, collecting the reflected lightand determining variations in time taken for the light to travel fromthe source to the detector.

Optionally, when the surgeon is satisfied with the targeting of thedevice, the surgeon initiates a command to the linear actuator 12 tomove with a predetermined speed to a predetermined depth from thesurface 32 of the tissue based on the reference heights of the tissuesurface 32 and the tip 26 of the implantation device 14. The speed anddepth of the implantation must be predetermined in a separate procedurethat is beyond the scope of this invention and is typically performed ineither a research environment on animal models or through extensiveimaging studies using technologies such as fMRI (function magneticresonance imaging). In the embodiment shown in FIG. 3, the maximum speedis 200 m/s with a positional accuracy of 10 microns. During implantationthe signals from the load cell 20 and the contact sensor 16 are used tocontrol the trajectory of the actuator and compensate for the differencebetween predicted insertion forces and contact points and measuredinsertion forces and contact points. The algorithm for controlling thetrajectory of the actuator is laid out in FIG. 12.

Step 31: At this step, the actuator 12 is at the optimal implantlocation, the tissue height has been referenced and the laser rangingsub-system 30 has a measure of the dynamic distance from the tissuesurface 32 to the tip 26 of the device 14 to be implanted, based on themotion of the tissue surface 32 due to pulsatile and respiratory motions

Step 32: The surgeon or processor 40 initiates the implantationprocedure and the actuator 12 moves toward the tissue surface 32 at apredefined speed that incorporates the dynamic motion of the tissue.

Step 33A: The contact sensor 16 detects contact and signals theprocessor 40.

Step 33B: The load cell 20 detects the force the tissue is exerting onthe device 14 during implantation and signals the processor 40.

Step 34A: The processor 40 compares the actual distance the actuator 12travelled when contact was detected to the expected value based on thetissue reference height and the length D₂ of the device 14 to beimplanted.

Step 34B: The processor 40 compares the actual force on the device 14being implanted to the expected force.

Step 35: The processor 40 adjusts the speed of the actuator 12 and theremaining distance it will travel to reach the implantation depth basedon the output of Step 34A and 34B.

Step 36: The final travel distance of the actuator 12, the contactheight and the load cell output are stored in memory 42 for diagnosticpurposes.

Step 37: Once implantation is completed, the clamp mechanism 18 releasesthe clamping surface 22 and the actuator 12 retracts to its homeposition in anticipation of the next device 14 being used.

Another embodiment of the invention monitors body function and movement(e.g., breathing, pulse, muscle twitching or spasms, etc.) of thepatient and the target tissue's relative movement to the device 14 as afunction of the body function and movement. The aforementionedsub-systems (laser ranging sub-system 30, imaging sub-system 28) of theapparatus 10 can be used as monitors, but any commercially availablecomponent that performs such monitoring tasks is acceptable. Theprocessor 40 will analyze the body functions and movements to generate adynamic system equation or equations to synchronize the actuation of theactuator 12 for placement of the device 14 into the tissue.

While the disclosure has been described in detail and with reference tospecific embodiments thereof, it will be apparent to one skilled in theart that various changes and modifications can be made therein withoutdeparting from the spirit and scope of the embodiments. Thus, it isintended that the present disclosure cover the modifications andvariations of this disclosure provided they come within the scope of theappended claims and their equivalents.

What is claimed is:
 1. A method to insert a device into tissue of apatient, the method comprising the steps of: a. loading the device forimplantation into a clamping mechanism connected to an actuator, whereinthe device comprises one or more implantation shanks that will form oneor more implantation sites on the tissue when implanted into the tissue;b. referencing a position of the device with respect to the actuator; c.locating an implantation vicinity of the tissue; d. identifying aninitial implantation location within the implantation vicinity; e.capturing a raw image of a field of view of the implantation vicinity,wherein the initial implantation location is contained within the fieldof view; f. referencing a surface of the tissue in the field of viewwith respect to the actuator; g. analyzing a portion of the raw imagecontaining the initial implantation location to generate a map ofsensitive structures in the tissue that could be damaged by the one ormore implantation shanks of the device at the initial implantation sitesduring implantation to form one or more initial implantation sites; h.comparing the one or more initial implantation sites of the device withthe map of the sensitive structures in the tissue to determine severityof damage to the tissue; i. virtually reorienting the one or moreinitial implantation sites to one or more subsequent implantation sitesto form a subsequent implantation location; j. comparing the one or moresubsequent implantation sites of the device with the map of thesensitive structures in the tissue to determine severity of damage tothe tissue; k. repeating steps i and j until every horizontal andangular position in the field of view has a computed severity of damageto form a plurality of severity of damage calculations; l. identifyingan optimal implantation location from the plurality of severity ofdamage calculations; m. adjusting the device to the optimal implantationlocation; n. actuating the device to be implanted along a single,longitudinal axis toward the optimal implantation location through adistance that is determined based on a depth of the device in the tissueand the instantaneous distance between the actuator and the surface ofthe tissue; o. detecting an actual point and an actual time of contactbetween the surface of the tissue and the device; p. applying anadjustment to the distance the actuator will travel and a speed it istravelling based on a comparison of an expected point and an expectedtime of contact calculated using the referenced positions of theactuator and the tissue surface and a programmed speed of the actuatorand the actual point and the actual time of contact measured during theimplantation; q. measuring a force between the device and the surface ofthe tissue during implantation; r. applying an adjustment to thedistance the actuator will travel and the speed the actuator istravelling based on a comparison of an expected force duringimplantation based on experimental data for the tissue into which thedevice is being implanted and the actual force measured duringimplantation of the device; s. releasing the device that was implantedafter it has reached its target depth in the tissue by retracting theclamping surfaces from the device; t. retracting the actuator; and u.recording data that was collected during implantation of the device soit can be used for diagnostic purposes.
 2. The method according to claim1, further comprising the step of oscillating the device being implantedin a first direction coincident with the single, longitudinal axis and asecond direction normal/transverse to the single, longitudinal axisduring implantation of the device into the tissue, wherein a first and asecond direction oscillating frequencies are based on experimentallydetermined force reduction for the tissue into which the device is beingimplanted.
 3. An apparatus to insert a device into a soft tissue of apatient, the apparatus comprising: an assembly of a clamping mechanismfor retaining the device, wherein the assembly comprises an actuator foropening and closing a clamp having two opposing clamping surfaces tosecure the device therebetween and for controlling the insertion of thedevice into the soft tissue of the patient; an imaging subsystem fixedlyconnected to the assembly, wherein the imaging subsystem comprises amicroscope camera with several levels of magnification; a processor incommunication with the imaging system and the assembly, wherein theprocessor executes the following method steps comprising: positioning anend of the device in proximity of the soft tissue of the patient; takingan image of the soft tissue; processing the image and identifying animplantation location that will result in minimum amount of the softtissue damage during implantation; and inserting the device into theidentified implantation location.
 4. The apparatus according to claim 3,further comprising a coating on the clamping surface to reduce oreliminate sticking of the device to be implanted to the clampingsurfaces.
 5. The apparatus according to claim 3, wherein each clampingsurface of the two opposing clamping surfaces comprises a mating featureto hold and constrain the device to be implanted in a particularorientation and position with respect to an actuator that performs theimplantation.
 6. The apparatus according to claim 5, wherein the matingfeature is a projection.
 7. The apparatus according to claim 3, whereinthe actuator is capable of a single axis of actuation.
 8. The apparatusaccording to claim 3, wherein the actuator further comprises a rangingsubsystem, and the processor further executes method steps comprising:measuring a first distance between the actuator and a surface of thesoft tissue being implanted; calculating a second distance between a tipof the device to be implanted and the surface of the soft tissue;measuring a time-varying displacement of the surface of the soft tissueto be implanted; synchronizing motion of the actuator with thetime-varying displacement of the surface of the soft tissue; andinitiating a command to move linearly the actuator to a predetermineddepth from the surface of the soft tissue based on reference heights ofthe surface of the soft tissue, the tip of the device, and the surfaceof the soft tissue to be implanted based on the synchronized motion. 9.The apparatus according to claim 3, wherein the actuator furthercomprises a contact sensing subsystem, and the processor furtherexecutes method steps comprising: measuring a time of contact betweenthe device to be implanted and a moving surface of the soft tissue beingimplanted; calculation of a time difference between an expected momentof contact and an actual moment of contact between the device to beimplanted and a moving surface of the soft tissue; comparing the actualdistance the actuator traveled when the actual moment of contact wasdetected to an expected distance traveled based on a tissue referenceheight and a length of the device to be implanted; and adjusting a speedof the actuator and a remaining distance to be traveled by the actuatorfor the device to be implanted to reach a predetermined depth based on adifference between the expected moment and the actual moment of contactbetween the device to be implanted and the moving surface of the softtissue.
 10. The apparatus according to claim 3, wherein the actuatorfurther comprises a force feedback subsystem, and the processor furtherexecutes method steps comprising: measuring a force of resistanceexerted on the device being implanted by the soft tissue into which thedevice is being implanted; comparing an actual force on the device beingimplanted to an expected force; and adjusting a speed of the actuatorand a remaining distance to be traveled by the actuator for the deviceto be implanted to reach a predetermined depth based on a differencebetween the expected force and the actual force on the device beingimplanted.
 11. The apparatus according to claim 3, wherein themicroscope camera of the imaging subsystem is sensitive to differentspectral ranges including ultraviolet, visible and infrared.
 12. Theapparatus according to claim 3, further comprising a cassette incommunication with the processor, wherein the cassette holding aplurality of devices prior to implantation.
 13. The apparatus accordingto claim 3, wherein the step of processing the image and identifying animplantation location further comprises: processing the image todelineate tissue structures subject to damage by device implantation toform a processed image; overlaying on the processed image on a virtualrepresentation of implantation sites for which the device to beimplanted based on a horizontal and an angular position of the actuator;computing a total area of overlap between the virtual representation ofimplantation sites and the tissue structures subject to damage by thedevice implantation; displacing the virtual representation of theimplantation sites by a user-defined fraction of a dimension of a singleimplantation site and by a user defined step angle to subsequentimplantation locations to identify a set of horizontal and angularpositions; identifying an optimal implantation location based on thehorizontal and angular position of the implantation sites of the set ofhorizontal and angular positions that leads to the minimum overlap areabetween the implantation sites and the tissue structures subject todamage by device implantation; and moving the actuator to the optimalimplantation location.
 14. The apparatus according to claim 3, whereinthe step of inserting the device into the identified implantationlocation further comprises: a ranging subsystem for referencing thesurface of the soft tissue with respect to the actuator; a contactsensing subsystem for referencing the position of the device withrespect to the actuator and for detecting the contact of the device withthe soft tissue into which it is being implanted; and a referencing tabto which the device is contacted to reference its position with respectto the actuator.
 15. A method to insert a device into tissue of apatient, the method comprising the steps of: a. providing an imagingsystem comprising a camera; b. providing a device insertion systemcomprising an actuator; c. providing a processor in communication withthe imaging system and the device insertion system, wherein theprocessor executes the following method steps comprising: d. loading adevice for implantation into a clamping mechanism connected to anactuator, wherein the device comprises one or more implantation shanksthat will form one or more implantation sites on the tissue whenimplanted into the tissue; e. positioning the device in proximity of animplantation vicinity; f. capturing a raw image of a field of view ofthe implantation vicinity, wherein an initial implantation location iscontained within the field of view; g. identifying the initialimplantation location within the raw image of the field of view; h.analyzing the raw image to delineate tissue structures subject to damageby the one or more implantation shanks of the device duringimplantation; i. virtually reorienting the device to one or moresubsequent implantation locations and analyzing tissue structuressubject to damage by the one or more implantation shanks of the deviceat the one or more subsequent implantation locations; j. identifying anoptimal implantation location that leads to minimum tissue damage; k.adjusting the device to the optimal implantation location; l. actuatingthe device to be implanted along a single, longitudinal axis toward theoptimal insertion location through a distance that is determined basedon the desired depth of the device in the tissue and the instantaneousdistance between the actuator and a surface of the tissue; m. releasingthe device that was implanted in the tissue by retracting the clampingsurfaces from the device; and n. retracting the actuator.